Compositions incorporating a salt of monoester of citric acid and a method for synthesizing the monoester

ABSTRACT

A skin treatment composition comprising a physiologically acceptable carrier and 1-35% by weight of a salt of a monoester of citric acid. The skin treatment composition imparts a pleasant smoothness to the skin and may be incorporated in several products to treat skin dryness. The hydrophobic group having an ester linkage to citric acid has 10 to 18 carbon atoms. Monoester of citric acid may be synthesized with low levels of di- and triester by forming citric acid anhydride and reacting this to form the monoester.

This is a divisional application of Ser. No. 024,186 filed Mar. 10,1987, now U.S. Pat. No. 4,866,202.

The invention relates to compositions comprising effective amounts of asalt of a monoester of citric acid as skin-smoothing or softeningagents. Additionally, an improved method of synthesizing monoesters ofcitric acid is claimed.

BACKGROUND OF THE INVENTION

Many compositions used for treating human skin impart unpleasant feel tothe skin during or after use. Thus, many compositions containing soap,detergent or both and intended for cleansing the skin may dry the skinand leave it feeling rough, chapped and flaky. The drying effect ofthese compositions (which include toilet bars, liquid or powder handwashing and bubble bath compositions may be extremely pronounced incertain seasons, as in dry winter months. Use of such washingcompositions during these seasons may dry the skin to the point ofscaliness or brittleness, with resultant cracking, reddening, bleedingand soreness.

Other products applied to the skin such as shaving creams, foams or oilsmay also have a drying effect on skin. Moreover, the skin is stretched,scraped and often cut or punctured during shaving. These operationsaccompanying use of these products may exacerbate skin drying andincrease skin feeling of roughness, flakiness and brittleness.

Products for the treatment of skin dryness include oils, balms, creams,lotions, liniments, ointments, unguents and gels. While these productsmay moisten skin and reduce or reverse roughness, cracking andbrittleness of dry skin, many such products leave an unpleasant residuecausing the skin to feel sticky, stiff, inflexible and waxy or undulyoily and greasy. Other products which may leave an unpleasant residue onthe skin or which could benefit by improvement in skin treatmentqualities include insect repellent and bite compositions, antisepticsand skin burn compositions (for burns from heat, sun or wind).Additionally, compositions for chapped lips such as lip balm or creammay impart an unpleasantly waxy or greasy feeling to the lips.

Citric acid derivatives have been incorporated in a wide variety ofcompositions. A salt of a monoester of citric acid, made from citricacid and alkanols of 1-18 or alkenols with up to 10 carbon atoms, isused to stabilize vinyl halide polymers in U.S. Pat. No. 3,362,923(Kruth). Non-salt alkyl esters of citric acid in U.S. Pat. No. 3,929,712(Hiyama et al.) are said to impart lubricant properties to vinylchloride resins, each alkyl group having 12-22 carbons. Non-saltmonoesters of citric acid are said to deactivate metals in petroleumproducts, e.g. cracked gasolines, according to U.S. Pat. No. 2,747,979(Thompson). The radicals which esterify the citric acid may be alkyl orbenzyl.

Monoesters of citric acid have also been used in treating clothes, as inU.S. Pat. No. 3,754,860 (Frick, Jr. et al.) where citrate monoesterswith a small or moderate size aliphatic chain (up to 2-ethylhexyl) areincluded in wrinkle-resistant fabric finishes, and U.S. Pat. No.3,971,626 (Heyden et al.) where a citric acid ester with a fatty alcoholof 12-22 carbon atoms is incorporated in a leather-treating agent.Particularly disclosed in Hayden et al. are citric acid esters withstraight-chain unsaturated fatty alcohols and branched saturated orunsaturated fatty alcohols.

Monoesters of citric acid are also employed in the food technology art.U.S. Pat. No. 2,158,678 (Gooding et al.) describes agents said to retardthe development of rancidity and improve moisture retention inglyceridic oil compositions, e.g., margarine. These agents, defined atcol. 1, line 45 to col. 2, line 25, include monolauryl citrate andmonostearyl citrate. Related U.S. Pat. No. 2,523,792 (Vahlteich et al.)describes edible compositions which are said to retard rancidity inglyceridic oils and which have 15 to 37.5% of selected monoesters ofcitric acid (including monolauryl, monomyristyl, monopalmityl, monooleyland monostearyl citrate) dissolved in a solubilizing agent, e.g.,lecithin. Monoesters of citric acid are also said to retarddeterioration of milk and egg products in U.S. Pat. No. 2,667,419(Gooding et al.). Citric acid monoesters of decanols, dodecanols,hexadecanols, and octadecanols are particularly disclosed and moreparticularly monolauryl and monostearyl citrate. Also, U.S. Pat. No.2,902,372 (Harris) discloses monoesters of citric acid with aliphaticalcohols of less than 3 carbon atoms for the purpose of improving thewhipping properties of egg whites. Finally, U.S. Pat. No. 3,004,853(Julian et al.) discloses citric acid esterified with cetyl alcohol aspart of an emulsifier system in a liquid shortening.

Other emulsifiers derived from citric acid, useful in the foods industryor cosmetology, are disclosed in U.S. Pat. No. 3,929,870 (David et al.).Specific citric acid derivatives in cosmetics include certain triestersof citric acid for shampoos disclosed in U.S. Pat. No. 4,176,176 (Cella)and 1-25% of citric or acetylcitric acid esterified by aliphaticalcohols having 1-6 carbon atoms for deodorant sticks and spraysdisclosed in U.S. Pat. No. 4,010,253 (Reese et al.). European Patent8105 (BASF) describes cosmetic preparations having 4-40% of citric acidesters carrying branched-chain alcohol radicals having 8-13 carbon atomssuch as Tris-isodecyl citrate. German Patent No. 2,361,716 (Henkel)describes cosmetic preparations having 0.5-15% of coesters made from a)aliphatic diols, b) citric or acetylcitric acid, and c) aliphaticmonofunctional alcohols having 12-30 carbon atoms. Preparationsincorporating the coester are said to be soft and to produce nounpleasant feeling of sticking to the skin.

Citric acid or its derivatives have also been incorporated in toiletbars. Romanian Patent No. 72,330 (Grigorescu) describes incorporatingcitric acid in a cosmetic soap. U.S. Pat. No. 4,292,192 (Hooper) statesthat incorporating 0.3 to 3% of citric or acetylcitric acid esterifiedby an alkyl group of 1 to 4 carbon atoms imparts a deodorancy propertyto personal washing bars. (Another monoester incorporated in a personalwashing composition, although not a citric acid derivative, isROOC-(CH₂)_(n) -COOM, where R is an alkyl or alkenyl chain with 4-12carbon atoms, n=2-4 and M is a cation disclosed in the currently pendingU.S. patent application of Nambudiry et al., Ser. No. 914,022, filedOct. 1, 1986 for Detergent Compositions.)

Citric acid derivatives have also appeared in detergent compositions aspollution control substitutes for other components. Thus, U.S. Pat. No.3,816,318 (Hentschel) discloses washing, dishwashing and cleaningdetergent compositions which include 5 to 30% of salts of certainmonoesters derived from polybasic carboxylic acids and alcohols of atleast 1 hydroxyl group and 1-8 carbon atoms. Hentschel states that owingto strengthened lipophilicity, the monoesters have heightenedemulsifying properties. Specific monoester salts are disclosed.

U.S. Pat. No. 4,271,032 (Kolaian et al.) discloses compositions forremoving soil from fabrics in laundering. The compositions includemonoesters of certain polycarboxylic acids, the alcohol radical having12-30 carbon atoms. The monoesters are said to be effective as asurfactant or as a builder. European Patent No. 199,131 (Raffineria OliiLubrificanti), published Oct. 29, 1986, describes surfactants derivedfrom citric acid, namely citric acid mono-, di- and triesters withalkoxylated alcohols described therein. Mixtures of these esters aresaid to be very efficient surfactants with excellent detergent andbiodegradability properties and with little or no toxicity or skinirritancy. Mixtures of the esters are also said to be suitable for aliquid detergent for kitchenware as well as liquid or creamy skindetergents or bath foam, as set out in the Examples.

It has been discovered that salts of certain monoesters of citric acidimpart desirable qualities to skin treatment compositions.

Some conventional methods of synthesizing monoesters of citric acidyield a mix of mono-, di., and triesters of citric acid. The mixedmono-, di- and triester products of these methods is impractical in manyapplications. Only the monoester is soluble in alkaline aqueous systems.Additionally, the di- and triesters severely limit foaming. Thus, itwould be desirable to produce monoesters of citric acid in a pure form,or in such predominance that the problems due to di- and triesters wouldbe insignificant.

In the first of these methods, citric acid is reacted directly with analcohol: the blend is heated, agitated until a solid forms, and cooledunder reduced pressure, as described in U.S. Pat. Nos. 2,523,792(Vahlteich) and 3,929,870 (David et al.).

A second method involves mixing citric acid in a dioxane solvent andadding an alcohol. The reaction mixture is refluxed for up to 72 hours,then the dioxane evaporated under reduced pressure. The remainingresidue is diluted, then is stripped at 60° C. under reduced pressure.This method is described in U.S. Pat. No. 4,271,032 (Kolaian et al.).The yield of monoester of citric acid from both these directesterification methods is about 60%. It is noted that dioxane is notonly an expensive solvent; its use may be accompanied by peroxidecompounds which, upon accumulation, may be explosive.

While the methods of synthesizing monoesters of citric acid produce amixture of mono-, di- and triesters, the relative molar amounts ofcitric acid and alcohol affect whether the mono, di- or triester productpredominates. Thus, reacting substantially equal molar amounts of citricacid and alcohol (or a greater amount of the former) favors monoester,while diester predominates when a molar amount of alcohol double that ofcitric acid is used.

One process which exploits this effect is described in U.S. Pat. No.2,518,678. Citric acid is dissolved in dry pyridine. Stearyl alcohol isadded to the solution and heated for 20 hours. Since only a smallconcentration of stearyl alcohol is said to be soluble in the pyridinesolution, a small concentration of the alcohol is continually reactedwith a large concentration of citric acid, favoring monoester formation.

However, even this process produces a mixture of mono-, di- andtriesters, requiring expensive and cumbersome steps to purify themonoester such as the techniques of fractional crystallization andselective extraction with suitable solvent systems described in U.S.Pat. Nos. 2,518,678 and 2,523,792.

A. J. Repta et al., "Synthesis, Isolation, and Some Chemistry of CitricAcid Anydride", Journal of Pharmaceutical Sciences 58, (September 1969),pages 1110-1114, describes synthesis of citric acid anhydride at page 1,col. 2, lines 14-31 and page 2. Suggested uses of the anhydride are as adessicant or an ingredient in formulations for carbonation.

In the Nambudiry application cited above, monoesters are prepared bymixing and heating an acid anhydride, e.g. succinic anhydride, withfatty alcohol.

It has been discovered that monoesters of citric acid may be producedwith minimal levels of di- and triester if citric acid is first reactedto form citric acid anhydride then reacted to form the monoester.

SUMMARY OF THE INVENTION

This invention embraces a composition and a process. The processconcerns synthesis of particular compounds, i.e., monoesters of citricacid, while the composition concerns salt forms of those compounds.Thus, while synthesis of, for example, monododecyl citrate via the stepsdescribed below falls within the process of the invention, it isincorporation of a disalt such as disodium salt of monododecyl citrateinto a physiologically acceptable carrier which comes within thecomposition part of the invention.

The composition aspect concerns a skin treatment composition comprising1-35% of a salt of a monoester of citric acid and a physiologicallyacceptable carrier. It has been discovered that this composition has thedesirable quality of imparting to skin a marked smooth and creamy feel.It has further been discovered that toilet bars incorporating a salt ofa monoester of citric acid themselves have an unusually pleasantsmoothness and slip.

The salt of the monoester of citric acid has one of the followingformulae: ##STR1## R₁ has the structure of a moiety derived from R₁ -OH,which alcohol is selected from the group consisting of alkanols, alkenoland arylalkanols having 10 to 18 carbon atoms. Each M is a cationindependently selected from the group consisting of alkali metals,alkaline earth metals, ammonium and substituted ammonium.

Skin treatment compositions incorporating 1-35% of a dication salt of amonoester of citric acid ester may be toilet bars, liquid hand washingcompositions, shaving cream, antiseptics, insect repellent or bitecompositions, and skin treatment compositions for dry, rough, or chappedskin or skin burned by heat, sun or wind.

The skin treatment composition of the instant invention may be in theform of a cream, liniment, oil, balm, ointment, solution, gel or unguentand may be applied directly to the skin. Incorporation of suchcompositions in pads, plasters, bandages, dressings, and pre-moistenedtowelettes, all optionally carrying medication in addition to the skintreatment composition, results in product embraced by this invention.

Without in any way limiting the scope of the present invention to thefollowing theoretical considerations, applicant would like to emphasizehis belief that it is the salt of the monoester of citric acid (ratherthan any di- or triester which may be present at very low levels) whichcontributes to the smoothening effect of the skin, and that maximizingthe level of the monoester salt in skin treatment compositions resultsin markedly improved products. Moreover, it is important that the R₁chain of the monoester be long enough to impart adequate hydrophobicityto the composition and to produce the smoothness and slip of suchcompositions. Consequently, it is monoesters having higher R₁ chainlengths which are included in the skin treatment compositions of theinvention. These R₁ chains are typically straight chains, i.e.,unbranched and not alkyl substituted.

The process aspect of this invention concerns synthesis of monoesters ofcitric acid. Pure or predominantly monoester is desirable for reasonsstated above. It has been discovered that monoesters of citric acid maybe synthesized with minimal production of di- or triesters: about 95% ofthe esterified citric acid is in monoester form, the balance being anacetyl derivative of the monoester. This new synthetic process produceshigher yields in less time (75% and above in less than 12 hours) of anearly pure monoester, and avoids the expense and difficultiesassociated with the solvent dioxane and purification of the monoesterfrom the di- and triesters.

The process comprises heating citric acid with an organic anhydride toform citric acid anhydride. Then an alcohol of the formula R₁ -OH isadded to the reaction mixture, R₁ -OH being defined as above. Thereaction mixture is then continually distilled under reduced pressure toremove volatile materials such as liberated short chain acid sideproducts. The monoester product may then be isolated as a dication saltand, if desired, isomers I and II may be purified. The isomer of formula(II) predominates in the product of this method by about a factor of 3,while the isomer of formula (I) predominates in the product of directesterification by about a factor of 3.

DETAILED DESCRIPTION OF THE INVENTION

In its composition aspect, this invention relates to skin-smoothingcompositions, which comprise, in admixture with a pharmaceuticallyacceptable carrier vehicle, an effective amount of a salt of a monoesterof citric acid having one or both of the following formulae: ##STR2##where R₁ is derived from R₁ -OH, which alcohol is selected from thegroup consisting of alkanols, alkenols and arylalkanols having 10 to 18carbon atoms; and

where M is a cation selected from the group consisting of alkali metals,alkaline earth metals, ammonium and substituted ammonium, particularlyincluding mono., di-, and trialkanol ammonium.

Compositions of this invention include a salt of an ester of citricacid. This ester of citric acid may consist essentially of the monoesterof citric acid or may comprise a mixture of mono-, di- and triesters ofcitric acid.

The compounds of formulae (I) and (II) are isomeric forms of a salt of amonoester of citric acid, (II) being a symmetrical and (I) anasymmetrical isomer. Compositions of the present invention may haveeither isomer or a mixture of both. In a preferred embodiment, when bothisomers are present, the relative amount of (II) to (I) may be about b3:1. Additionally, the monoester salts of citric acid need not all haveidentical R₁ groups. Furthermore, each molecule of the salt of amonoester of citric acid may have two of the same or different cations;if all the salt molecules have the same cations, the cations need not bethe same from molecule to molecule.

R₁ may more particularly have the structure of a moiety derived from R₁-OH, which alcohol is selected from the group consisting of straightchain alkanols and alkenols having 10 to 18 carbon atoms; or consistingof alkanols and alkenols having 12 to 15 carbon atoms. One commerciallyavailable mixture of alkanols which is suitable for esterifying citricacid has primary alcohols with 14 to 15 carbon atoms, sold as NEODOL 45.The NEODOL products are available ex Shell Oil Company, One Shell Plaza,Houston, Tex. 77002.

Instead of the 1 to 35% of a salt of a monoester of citric acid, thecomposition of the inventions may more particularly include from 5 to30% or from 10 to 25% of the salt of a monoester of citric acid. Atlevels over 35%, compositions which are intended to be solid may becomesoft, mushy and pliable. (All component amounts expressed in percentagesindicate percent weight unless otherwise stated.)

The compounds of formulae I and II may be incorporated in aphysiologically acceptable carrier of petroleum jelly, lanolin, paraffinwax, alkanols, water and mixtures thereof as well as the carriers of theexamples below. More particularly, the water may be a 1-5% solution ofan appropriate buffer, such as sodium bicarbonate. The physiologicallyacceptable carrier may comprise soap or detergent toilet bars, or liquidor powder hand washing compositions, antiseptics, insect repellent andbite compositions, shaving creams, oils and foams, and compositions fortreatment of dry, rough or chapped skin. Some formulations of thecomposition may be applied briefly and washed off, as in washing handswith a toilet bar within the invention, while other formulations such asa cream or ointment described below, may be left on indefinitely.

The skin treatment composition of the present invention may take any ofthe following forms: lotion, liniment, solution, suspensions, oil,ointment, cream, gel, balm, unguent, paste, stick or aerosol and may beapplied directly to the skin. Application may also take place in usingone of the consumer products listed above, e.g. in washing hands with atoilet soap bar. Alternatively, the skin treatment composition of thisinvention may be incorporated in pads or pre-moistened towelettes for awiping application to the skin or onto bandages, dressings or plastersfor a longer application. The bandages, dressings, pads, plasters andpre-moistened towelettes may be optionally medicated with substances inaddition to the skin treatment composition.

Conventional soap compositions typically are comprised of from 25 to 90%by weight of soap and from 1 to 15% water. When such compositionsfurther incorporate salt of monoester of citric acid within one of theabove-recited ranges, the compositions come within the presentinvention. The term "soap" is used herein to mean the alkali metal oralkanol ammonium salts of aliphatic alkane, or alkene monocarboxylicacids having about 12 to about 20 carbon atoms, and preferably about 12to 18 carbon atoms.

It is preferred to use soaps having the fatty acid derived from coconutoil, tallow, or mixtures thereof, since these are among the most readilyavailable fats. The proportion of fatty acids having at least 12 carbonatoms in coconut oil soap is about 85%. This proportion will be greaterwhen mixtures of fatty acids derived from fats such as tallow, palm oil,or non-tropical nut oils or fats are used, wherein the principal chainlengths are of sixteen carbon atoms or more. The tropical nut oilsinclude: palm kernel oil, babassu oil, ouricuri oil, tucum oil, cohunenut oil, murumuru oil, jaboty kernel oil, khakan kernel oil, dika nutoil, and ucuhuba butter. A preferred soap for use in the compositions ofthis invention has at least about 85% fatty acids having 12-18 carbonatoms.

Derivation of fatty acids from oils and fats for use in this inventionis by known methods, e.g., saponification of said oil or fat.

An especially preferred soap composition comprises a mixture of alkalimetal salts of fatty acids of which 10 to 70% are derived from coconut,and 90 to 30% are derived from tallow. More particularly, 15 to 20% ofthe fatty acids may be derived from coconut oil and 75 to 85% fromtallow. These mixtures contain about 95% fatty acids having 12 to 18carbon atoms.

Additionally, optional ingredients may be included in soap formulationsof the present invention, e.g., free fatty acids, emollients, sudsboosting agents, germicides, opacifiers (such as titanium dixoide) andcolorants, pigments, perfumes, preservatives, electrolyte salts andmixtures thereof. A typical listing of the classes and species ofoptional ingredients useful in soap compositions appears in U.S. Pat.No. 4,260,507 incorporated herein by reference. It should be understood,of course, that these lists of optional ingredients and mixtures forsoap compositions are only representative of such materials and is notintended to be limiting.

The soap compositions of the present invention may be in liquid or solidform. The latter form is well known commercially as the toilet bar.Requirements for a good toilet bar are well known and enumerated in U.S.Pat. No. 2,894,912. The properties of soap toilet bars of the presentinvention are similar to those of conventional bars with the addition ofproperties herein disclosed.

Soaps and Detergents, Thomssen and McCutcheon, MacNair-Dorland Company,1949, pp. 195-207 and Kirk-Othmer Encyclopedia of Chemical Technology,John Wiley & Sons, 1983, Vol. 4, pp. 173-177 describe techniques oftoilet bar-making including milling, plodding, framing and shaping, bymeans of which the soap compositions of this invention may be shapedinto bars. A bar of toilet soap may be formed by these techniques fromthe following composition: about 80% of fatty acids derived from tallowand coconut, about 10% water and about 10% of disodiummonododecylcitrate. The bar itself has a remarkable smoothness and slip;washing with one's skin with the bar imparts a pleasant smoothness tothe washed skin.

Non-soap skin-cleansing compositions may also come within thisinvention. These skin-washing compositions, with detergent activecompounds replacing all or part of the soap in the toilet soap bars, arecomprised of from about 10% to about 70% by weight of a detergent activecompound, about 2% to about 20% suds booster, about 10% to about 40% byweight aliphatic fatty acid, about 2.5% to about 25% by weightwater-soluble aliphatic fatty acid soap, about 1% to about 35% by weightof a salt or salts of monoester of citric acid and about 1% to about 10%by weight water. Additionally, the optional ingredients which may beincluded in these compositions are the same as those listed above forsoaps.

Examples of detergent active compounds usable to form these compositionsare found in "Surface Active Agents" by Schwartz & Perry (Interscience1949) and "Surface Active Agents" by Schwartz, Perry & Berch(Interscience 1958) and those set forth in U.S. Pat. No. 2,894,912 andU.S. Pat. No. 3,070,547, each of which is hereby incorporated byreference. More particularly, the detergent active may be selected fromthe group consisting of alkali metal, magnesium or ammonium salts ofdetergents selected from the group consisting of C₁₂ -C₁₆ hydroxyalkanesulfonates, C₈ -C₁₈ N-acyl taurates, C₁₂ -C₁₈ alkyl sulfates, C₁₂ -C₁₈alkyl ether sulfates, C₁₂ -C₁₆ alkyl phosphonates and phosphates, C₁₂-C₁₆ mono-alkyl succinates and maleates, C₆ -C₁₄ dialkylsulfosuccinates,C₁₆ -C₂₀ alkane disulfonates, C₈ -C₁₈ alkene sulfonates, alkylbenzenesulfonates and mixtures thereof. Further, the detergent active may be analkali metal, magnesium or ammonium salt of a fatty acyl ester ofisethionic acid, in particular fatty acyl esters derived from fattyacids having from 10 to 18 carbon atoms; more particularly the fattyacyl groups may be derived from fatty acids derived from coconut oil.

These skin cleansing compositions ma be liquid or solid. The solidcompositions may be formed into toilet bars according to the steps setforth in Thomssen and McCutcheon for soap bars. The properties of thedetergent toilet bars of the present invention are similar to those ofsoap bars as well as to those of conventional bars with the addition ofproperties herein disclosed.

Skin-cleansing compositions of the present invention may incorporatesoap or detergent active compounds or both. In addition to 10-35% of oneof the soaps or detergent active compounds discussed above, or a mixtureof both, a liquid hand cleansing composition of the present inventioncomprises 1 to 35% of a salt of a monoester of citric acid, 0-5% sodiumchloride, and balance water. Optionally, this composition may furtherinclude 1-5% of a suds boosting agent, for example, cocomonoethanolamide and 0.2-0.5% of a preservative, for example, EDTA.

When the composition of this invention is a toilet bar or liquid handcleansing composition, it is desirable that little or no triester orsalt of diester of citric acid be present, as these have been found tolimit foaming and are insoluble in alkaline aqueous systems.

Shaving creams within the present invention comprise 1 to 35% of a saltof a monoester of citric acid, 25-50% stearic acid, 5-20% coconut oil,10-25% glycerol, 1-15% mineral oil and 5-45% water.

A composition for treating dry, rough or chapped skin such as chappedlips under the present invention may be in solid form for use as astick-type composition. Such compositions comprise from 1 to 35% of asalt of a monoester of citric acid, and from 50% to 98%, preferably 60%to 90%, of an emollient. This composition may further comprise from 1%to 20%, preferably 5% to 15%, of a suitable thickening agent, andoptionally emulsifiers and water.

A typical listing of suitable thickening agents, emollients andemulsifiers useful in solid compositions appears in U.S. Pat. No.4,560,549 (Ritchey et al.) incorporated herein by reference. It shouldbe understood, of course, that the list of optional ingredients andmixtures there described is representative only and is not intended tobe limiting. Additives commonly found in topical compositions such aspreservatives, e.g. methyl and ethyl paraben, dyes and perfumes areadvantageously included in any of the above-described solid compositionsfor treating dry, rough or chapped lips.

Compositions for treating dry, rough or chapped skin further may be inointment form comprising 1 to 35% of a salt of a monoester of citricacid, 1 to 5% anhydrous wool fat, 5 to 20% viscous paraffin, 0 to 5%cetyl alcohol and 65-95% white petroleum jelly. More particularly, thecetyl alcohol may be present at 0.5-2.5%.

When the skin treatment composition of the present invention is in creamform, it comprises 1 to 35% of a salt of a monoester of citric acid,from 50 to 5%, preferably 25 to 10% of an emollient, and the balancewater. Optionally, the cream form contains a suitable emulsifier. Theemollients and emulsifiers described above for compositions of theinvention in stick form are equally suitable here.

The compositions of this invention may also be formulated in solutionform, comprising from 1 to 35% of a salt of a monoester of citric acid,and 65 to 99% of a suitable organic solvent. Suitable organic materialsuseful as the solvent or a part of a solvent system are as follows:propylene glycol, glycerine, ethanol, sorbitol esters,1,2,6-hexanetriol, isopropanol, diethyl tartrate, butanediol, andmixtures thereof. Such solvent systems can also contain water.

The compositions of this invention may also be formulated in aerosolform by incorporating the solution formulation described above in aclosed metal container fitted with an aerosol cap and pressurized usingconventional methods at from 25 psi up to 100 psi pressure with anaerosol propellant such as butane gas.

In a gel form, the present invention comprises 1 to 35% of a salt of amonoester of citric acid, 5 to 75% and preferably 10-50% of an organicsolvent, 0.5 to 20%, preferably 1 to 10% of a thickening agent, thebalance being water. Suitable thickening agents include those recitedabove for compositions in solid form. Suitable organic solvents includebut are not limited to glycerine, sorbitol esters, 1,2,6-hexanetriol,ethanol, isopropanol, diethyl tartrate, butanediol, and mixturesthereof.

The process aspect of this invention concerns synthesis of monoesters ofcitric acid. The process comprises mixing citric acid with an organicanhydride of the formula (III): ##STR3## where R₂ and R₃ areindependently selected from the group consisting of hydrocarbon chainshaving from 1 to 5 carbon atoms or, with R₂ and R₃ taken together,containing 6 to 8 carbon atoms linked to form a cycloaliphatic oraromatic anhydride or substituted derivative thereof. More particularly,the anhydride may be acetic anhydride. The amount in moles of anhydrideadded is substantially equal to or slightly greater than the amount inmoles of citric acid.

In a preferred embodiment, the citric acid and anhydride reactionmixture is heated to a temperature of from 60° C. to 90° C. for 15 to 45minutes, producing citric acid anhydride, which is believed to have oneof the following formulae: ##STR4##

Regardless of the structure of any product or intermediate in thereaction mixture at this stage, an alcohol of the formula R₁ -OH may beadded directly to the reaction mixture, R₁ -OH being selected from thegroup previously defined. The amount in moles of alcohol added issubstantially equal to or slightly less than the amount in moles ofcitric acid used to form the initial reaction mixture.

The citric acid anhydride and alcohol are subjected to heat andcontinuous distillation under reduced pressure to remove volatiles andproduce predominantly the monoester of citric acid. In a preferredembodiment, the reaction mixture is heated to 60°-80° C. andcontinuously distilled at reduced pressure for 5-10 hours.

The monoester is in solution at this point. To isolate the monoester asa dication salt, the solution is cooled, diluted and neutralized with anorganic or inorganic base. For example, the solution may be cooled toroom temperature (25° C.) or below, diluted with a solvent such asethanol or methanol, then neutralized to a pH of about 6.0 to about 8.5with the solution at 15° C. or below. Organic or inorganic bases such assodium hydroxide, potassium hydroxide, ammonia solutions, ammonium orsubstituted ammonium (particularly monoethanolamines), or salts thereof,alkali metal carbonates or alkaline earth metal carbonates orbicarbonates, or mixtures thereof may be used to neutralize thesolution. The choice of the neutralizing reagent is governed by whichsalt or salts of the monoester of citric acid one wishes to form, sincethe cation of the neutralizing reagent becomes the cation of themonoester salt. The solid precipitate which forms is the salt of amonoester of citric acid of formula (I) or (II) above.

Alternatively, in another reaction mode, the citric acid may initiallybe placed in a solvent, such as acetone or an acid of the formula R₄-COOH, where R₄ is selected from the group consisting of hydrocarbonatoms having from 1 to 5 carbon atoms. An amount in moles of organicanhydride of the above formula (V) substantially equal to or slightlygreater than the amount in moles of citric acid is added to thesolution. The remainder of the steps are similar to those above.

Preferably, the citric acid used to form the monoester is anhydrous, toprevent lower yields due to hydrolysis of the anhydride reagent by waterwhich may otherwise be present. Solvents employed for the citric acidpreferably are also anhydrous.

It is an advantage of this process that predominantly monoesters areproduced, i.e. about 95% of the esterified citric acid, the balancebeing an acetyl derivative of the monoester and minimal levels of di-and or triesters of citric acid. The synthesis of the present inventionthus produces nearly pure monoester of citric acid.

Like the conventional direct esterification methods, the instantsynthetic method yields a mixture of symmetrical and unsymmetricalisomers of citric acid monoester. However, the two methods yieldrelatively different isomeric products: the anhydride synthesis yieldsmainly symmetrical isomer predominating by about a factor of three overthe unsymmetrical ester, while direct esterification yields mainlyunsymmetrical ester predominating by roughly the same factor.

These isomers may be isolated from one another by known methods, amongwhich are re-crystallization techniques. A preferred approach forisolating the symmetrical isomer of citric acid monoester from theunsymmetrical isomer follows: the monoester may be dissolved in asolvent system comprising 9 parts heptane and two parts ethyl ether.Adding an additional 1.5 parts ethyl ether induces precipitation. Onceprecipitation is complete, the solution may be filtered yielding puresymmetrical ester with melting point of 78°-80.5° C.

In addition to the two isomeric forms of the monoester of citric acid,the citric acid anhydride process may form small amounts of diesters.However, the second ester linkage of this diester forms at the hydroxylgroup of citric acid rather than at one of the carboxyl groups. Thediesters apparently result from the reaction of the citric acid hydroxylgroup with the short chain organic anhydride, the acid solvent, whenused, or with the acid formed from hydrolysis of the anhydride. Thus,when acetic anhydride reactant for example is used to form citric acidanhydride, there may be formed some acetyl ester of citric anhydride.Subsequent reaction of the latter compound with long chain alcohols, forexample, leads to formation of diesters. Such compounds usually compriseless than 10% of the citric acid monoester product and often comprisefar less than 50%.

For a further understanding of this invention, reference may be made tothe following examples:

EXAMPLE I

A toilet soap bar having the following composition is made by mixing thefirst three components in a Brabender kneader for 35 minutes at 50° C.then adding the last two components and mixing for 10 minutes more:

Disodium salt of monododecylcitrate 17.6

Mixture of sodium salts of fatty acids, of which 82% are 76.5% derivedfrom tallow and 18% are derived from coconut oil:

Water: 3.8%

TiO₂ : 1%

Perfume: 1%

EXAMPLE II

A toilet soap bar is made having the following composition by the stepsof Example I:

Disodium salt of the monoester of citric acid derived 20% from primaryalcohols having 14 to 15 carbon atoms:

Mixture of sodium salt of fatty acids of which 82% are 70% derived fromtallow and 18% from coconut oil:

TiO₂ : 1%

Perfume: 1%

Water: balance

The bars of Examples I and II impart a creaminess and smoothness to skinwashed with the bars. Additionally, the bars themselves have a markedlypleasant smooth hand feel.

EXAMPLE III

A detergent toilet bar is made having the following composition: 10% ofdipotassium salt of citric acid monoester esterified with primaryalcohols having 14 to 15 carbon atoms, 9% water, 50% of disodium salt oflauroyl ester of isethionic acid, 10% unesterified sodium salt ofisethionic acid, 10% of potassium lauryl sulfate as a suds-boostingdetergent salt, and 10% of paraffin wax as a binder-plasticizer. Thetoilet bar is formed by the conventional steps of toilet bar formation,and has the properties of the bars of Examples I and II.

EXAMPLE IV

A solid stick according to this invention containing a salt of amonoester of citric acid is prepared by shaping and molding thefollowing ingredients:

Disodium mono-n-decylcitrate: 20%

Lanolin wax: 65%

Glycerol: 5%

Methylcellulose: 5%

Water: balance

The resultant solid stick of this Example is applied upon the skin torelieve a feeling of dryness, roughness or scaliness.

EXAMPLE V

An ointment formulation is prepared by thorough mixing of the followingingredients.

Dipotassium salt of a monoester of citric acid 20% esterified with C₁₄-C₁₅ primary alcohols:

Anhydrous wool fat: 2%

Viscous paraffin: 10%

White petroleum jelly: balance

The resultant ointment is applied to the skin to relieve a feeling ofdryness, roughness or scaliness. Advantageously, the ointment is appliedevery four to twelve hours while dryness persists.

EXAMPLE VI

A cream is prepared by mixing the following ingredients together:

Disodium mono-n-tetradecylcitrate: 20%

Ethoxylated cholesterol: 20%

Sorbitol: 5%

Water: balance

The resulting cream is applied to the skin to relieve dryness in thesame manner as that described for the ointment in Example V.

EXAMPLE VII

A solution formulation is prepared by mixing the following components atroom temperature:

Glycerine: 60%

Disodium monolaurylcitrate: 15%

Water: balance

The solution is applied to affected skin in substantially the samemanner as that described for ointment in Example V.

EXAMPLE VIII

A gel formulation is prepared by mixing the following ingredients:

Disodium salt of monoester of citric acid 25% esterified with C₁₄ -C₁₅primary alcohols:

1,2,6-Hexanetriol: 45%

Bentonite: 8%

Water: balance

EXAMPLE IX

Anhydrous citric acid (0.2 moles) and acetic anhydride (0.24 moles)rapidly mixed then heated to 70° C. for 20-30 minutes. Lauryl alcohol(0.18 moles) is added to the reaction mixture, which is then subjectedto continuous distillation under reduced pressure at 70°-75° C. for 5hours to remove acetic acid.

The reaction mixture is cooled to 20° C. and diluted with ethanol, thenneutralized at 15° C. to pH of 8.5. Sodium carbonate (0.4 moles) isadded and the disodium salt of monododecyl citrate is recovered as aprecipitate.

EXAMPLE X

.Anhydrous citric acid (0.2 moles) is placed in a vessel and suspendedin acetic acid. Acetic acid anhydride (0.24 moles) is rapidly added tothe vessel and the mixture is heated to 80° C. for 30 minutes. A mixtureof saturated C₁₄ -C₁₅ aliphatic primary alcohols is added to the vessel.The reaction mixture is continuously distilled at reduced pressure at70° C. for 10 hours, the cooled to 25° C.

Ethanol (50 ml) is added to the vessel, then 50% aqueous NaOH is addedto neutralize the mixture to about pH 7. The disodium salts ofmonotetradecyl ester and monopentadecyl ester of citric acid arerecovered as precipitate.

In both of Examples IX and X, yields of the disodium salt of monoesterof citric acid are from 65% to 80%.

As will be readily apparent to persons of ordinary skill in the art towhich the present invention pertains, various modifications of suchinvention as hereinbefore set forth and as further defined in theappended claims may be made without departing from the spirit and scopethereof regardless of the applicability of the theoretical basesadvanced herein to elucidate of the invention.

What is claimed is:
 1. A skin treatment composition comprising fromabout 1% to about 35% by weight of a dication salt of a monoester ofcitric acid having one of the following formulae: ##STR5## where R₁ hasthe structure of a moiety derived from R₁ -OH, which alcohol is selectedfrom the group consisting of alkanols, alkenols an arylalkanols havingfrom 10 to 18 carbon atoms; each M is a cation selected from the groupconsisting of the alkali metals, the alkaline earth metals, ammonium,substituted ammonium and a mixture thereof; anda physiologicallyacceptable carrier for said monoester.
 2. The skin treatment compositionaccording to claim 1 wherein R₁ -OH is selected from the groupconsisting of straight hydrocarbon chain alkanols and alkenols havingfrom 10 to 18 carbon atoms.
 3. The skin treatment composition accordingto claim 1 wherein R₁ -OH is selected from the group consisting ofalkanols and alkenols having 12-15 carbon atoms.
 4. The skin treatmentcomposition according to claim 1 wherein R₁ -OH is lauryl alcohol. 5.The skin treatment composition according to claim 1 wherein themonoester of citric acid is comprised of symmetrical and unsymmetricalisomers in a relative ratio of about 3:1.
 6. The skin treatmentcomposition according to claim 1 wherein the skin treatment compositioncomprises a pharmaceutically acceptable carrier and from about 1 to 35%by weight of a salt of an ester of citric acid, the ester consistingessentially of the monoester of citric acid.
 7. The skin treatmentcomposition according to claim 1 comprising from about 5% to about 30%by weight of a salt of a monoester of citric acid, from about 25% toabout 90% by weight of soap, and the balance water.
 8. The soapcomposition according to claim 7 wherein fatty acids of the soap arederived from tallow.
 9. The soap composition according to claim 7wherein fatty acids of the soap are derived from a vegetable oil. 10.The soap composition according to claim 9 wherein the vegetable oil iscoconut oil.
 11. The soap composition according to claim 7 wherein fattyacids of the soap are derived from a mixture of tallow and coconut oil.12. The soap composition according to claim 11 wherein 10 to 70% byweight of the fatty acids are derived from coconut oil and 90 t 30% byweight of the fatty acids are derived from tallow.
 13. The soapcomposition according to claim 7 comprising about 10% disodium salt ofmonododecyl citrate, about 10% water and about 80% of a soap mixturecomprised of from 75% to 85% of an alkali metal salt of fatty acidsderived from tallow and from 15% to 25% of an alkali metal salt of fattyacids derived from coconut oil.
 14. The soap composition according toclaim 7 where the composition is formed into a toilet bar.
 15. The skintreatment composition according to claim 1 comprising 30 to 70% byweight of a detergent active compound, 2 to 20% by weight of a sudsbooster, 10 to 40% by weight of an aliphatic fatty acid, 2.5 to 25% byweight of a water-soluble fatty acid soap, 1 to 35% by weight of adication salt of a monoester of citric acid, and 1 to 10% by weight ofwater.
 16. A skin treatment composition according to claim 15 where thecomposition is formed into a toilet bar.
 17. The composition accordingto claim 15 wherein the detergent active compound is selected from thegroup consisting of alkali metal, magnesium or ammonium salts of C₁₂-C₁₆ hydroxyalkane sulfonates, C₈ -C₁₈ N-acyl taurinates, C₁₂ -C₁₈ alkylsulfates, C₁₂ -C₁₈ alkyl ether sulfates, C₁₂ -C₁₆ alkyl phosphonates andphosphates, C₁₂ -C₁₆ mono-alkyl succinates and maleates C₆ -C₁₄dialkylsulfosuccinates, C₁₆ -C₂₀ alkane disulfonates, C₈ -C₁₈ alkenesulfonates, alkylbenzene sulfonates and mixtures thereof.
 18. Thecomposition according to claim 15 wherein the detergent active compoundsare selected from the group consisting of alkali metal, magnesium orammonium salts of fatty acyl esters of isethionic acid.
 19. Thecomposition according to claim 15 wherein the fatty acyl portions of thefatty acyl esters is derived from fatty acids having 10 to 18 carbonatoms.
 20. The composition according to claim 19 wherein the fatty acylportion of the fatty acyl esters is derived from fatty acids derivedfrom coconut oil.
 21. The skin treatment composition according to claim1 comprising 10 to 35% by weight of a soap or a detergent compound or amixture of both, 1 to 35% by weight of a dication salt of a monoester ofcitric acid, 1 to 5% by weight of a suds-boosting agent, 0.2 to 0.5% byweight of a preservative and the balance water.
 22. The skin treatmentcomposition according to claim 1 comprising 25 to 50% by weight stearicacid, 5 to 20% by weight coconut oil, 10 to 25% by weight glycerol, 1 to15% by weight mineral oil, 5 to 45% by weight water and 1 to 35% byweight of a monoester of citric acid.
 23. The skin treatment compositionaccording to claim 1 wherein the physiologically acceptable carriercomprises an emollient.
 24. The skin treatment composition according toclaim 21 wherein the physiologically acceptable carrier comprises 50 to98% of an emollient and 1 to 15% of a thickening agent.
 25. The skintreatment composition according to claim 22 wherein the salt of amonoester of citric acid and the emollient are mixed and formed into asolid stick.
 26. The skin treatment composition according to claim 1 inointment form comprising 1 to 5% by weight anhydrous wool fat, 5 to 20%by weight viscous paraffin, and 65 to 95% by weight white petroleumjelly.
 27. The skin treatment composition according to claim 1 in creamform comprising 1 to 35% by weight of a salt of a monoester of citricacid, 5 to 50% of an emollient and 50 to 95% by weight water.
 28. Thecomposition according to claim 1 in solution form comprising 1 to 35% byweight of a salt of a monoester of citric acid and 65 to 99% by weightof an organic solvent suitable for solutions.
 29. The skin treatmentcomposition according to claim 26 where the composition is incorporatedin a closed metal container fitted with an aerosol cap and pressurizedat from 25 psi up to 100 psi pressure with a propellant.
 30. Thecomposition according to claim 1 in gel form comprising 1 to 35% byweight of a salt of a monoester of citric acid, 5 to 64.5% by weight ofan organic solvent suitable for gels, 0.5 to 5% by weight of athickening agent, and the balance water.